Interferon-.gamma. (hereinafter interferon is referred to as "IFN") is mainly produced by T-cells and is known to have three main functions, i.e., antiviral activity, anti-cell proliferation activity, and immunoregulation (reference 1). With the recent development in gene manipulation techniques, not only human IFN genes but also animal IFN genes, such as bovine, equine, and feline IFN genes have been isolated. Concerning canines, IFN-.alpha., .beta., and .gamma. have been reported (references 2 and 3). Compared with human or mouse IFN-.gamma., however, only a little knowledge has been obtained from in vitro and in vivo studies on canine IFN-.gamma., and there is no report using canine IFN-.gamma. as a therapeutic agent for any particular canine disease.
In humans, IFN-.gamma. has already been put into practical use as a therapeutic agent for malignant tumors. Concerning skin diseases, Hanifin et al. (reference 4) and Rheinhold et al. (references 5 and 6) reported its effectiveness for treating atopic dermatitis and steroid dependent asthma. There is doubt (reference 7), however, regarding the use of human IFN-.gamma. for human atopic dermatitis because of the following reasons: for effectively treating human atopic dermatitis with human IFN-.gamma., daily administration for 6 consecutive weeks or more is necessary; IFN-.gamma. has adverse effects such as fever and headache and gives the patients a rather large amount of stress while its effects are rather small; and IFN-.gamma. formulations are expensive.
Concerning human dermatitis, diagnosis criteria have been established (reference 8) and a genetic background is regarded as being an important criterion. In addition, human atopic dermatitis is known to be a type I allergic reaction, in which production of an excess amount of IgE in response to foods, animal scales, insect poisons, and the like is an important component (reference 9). However, there have not been any systematic studies done on canine atopic dermatitis. Therefore, the evaluation criteria are unclear and the relationship between the production of excess canine IgE and atopic dermatitis is not clear.
In general, canine skin diseases include eczema, urticaria, allergic dermatitis, traumatic dermatitis, mange, otitis externa, pruritic dermatitis, and the like. The following agents are conventionally used for the above diseases: antihistamines (diphenhydramines), antiphlogistics (dibucaine hydrochloride, etc.), insecticides, and bacteriocides (malathion, benzalkonium chloride, etc.), and steroids (dexamethasone, etc.).
Among therapeutic agents of the prior art used for treating canine skin diseases, however, there are disadvantages in the use of non-steroidal agents as their therapeutic effects are very low. Although steroidal agents have extremely strong pharmacological effects, they occasionally show adverse effects, such as enhancement of infection at disease regions and increases in vascular-wall fragility. Also, long-term administration of steroids may cause obesity or systematic adverse effects as a result of effects on other organs.
In general, canine skin diseases cannot be cured as well as those of humans because of inferior housing conditions. Thus dogs are frequently treated with repeated doses of the above therapeutic agents of the prior art. Treatment periods are thus extended, and occasionally, diseases are not completely cured even if treatment is continued for more than half a year. In some cases, treatment is extended for several years, resulting in great stress for the dog owner. Therefore, there is a demand for a therapeutic agent with a rapid and sustained effect on canine intractable dermatitis that cannot completely be cured by long-term treatment using therapeutic agents of the prior art.
Accordingly, an object of the present invention is to provide an effective therapeutic agent for canine intractable dermatitis.